The Jackson Laboratory Cancer Center (JAXCC) provides a unique concentration of genetic and genomic expertise focusing on applications of murine model systems and systems genomics in addressing cancer questions. The JAXCC has 47 members in one Research Program, Genetic Models for Precision Cancer Medicine, comprising 3 related themes in cancer cell robustness, genetic and genomic complexity, and progenitor cell biology. Collectively, we seek to determine the molecular drivers of intrinsic cancer resistance, cancer evolution, adaptation, and self-renewal. Innovations In genomic technologies, computational analytics and mouse models for human cancers are integral to all themes, providing a robust interdisciplinary structure. The JAXCC now operates on 3 campuses: JAX Mammalian Genetics (Bar Harbor, ME) with a focus on mouse models for complex genetics; JAX Genomic Medicine (Farmington, CT), with a focus on human cancer genomics; and JAX-West (Sacramento, CA) with a focus on pre-clinical trials using patient-derived-xenograft (PDX) mouse models of human cancer. The scientific leadership of JAX has direct oversight of the Cancer Center: Dr. Edison Liu is President and CEO of JAX and Director of the JAXCC. Dr. Robert Braun Is Vice President for Research of JAX and Deputy Director of the Cancer Center. Drs. Carol Bult, Chengkai Dai and Frank McKeon are co-programming Leaders. Associate Directors for Regional Translational Partnerships (Dr. Kevin Mills) and Research Administration (Dr. Barbara Tennent) expand the leadership structure. A dedicated 7-member External Advisory Board (EAB) advises them. The new leadership, combined with recruitment of new senior and junior investigators, and a significant increase in institutional resources for cancer research heightens the impact ofthe JAXCC. This has been realized In the expanded JAXCC translational outreach through regional and national partnerships (e.g., SWOG). Support is requested for Shared Resources: a) Computational Sciences, for advanced computational and statistical analysis; b) Genome Technologies, for innovations in next generation sequencing, and in metabolomic and proteomic analyses; c) Cancer Model Development for consultation and project management in developing new models; d) Genetic Engineering Technologies for manipulating germline and somatic gene expression in mice; and e) Phenotyping Technologies for microscopy, cytogenetics, clinical assessment, histology and flow cytometry. Funds are also requested for support of annual EAB meetings and JAXCC member retreats. Developmental funds significantly supplemented by institutional funds are requested for a pilot project program to stimulate new cancer research opportunities and for support of new investigators to the JAXCC.